Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview
The brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain’s principal fuel source. Glucose transport across the blood–brain barrier (BBB) is primarily controlled via sodium-indep...
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2019 |
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| author | Snehal Raut Aditya Bhalerao Michael Powers Minelly Gonzalez Salvatore Mancuso Luca Cucullo |
| author_facet | Snehal Raut Aditya Bhalerao Michael Powers Minelly Gonzalez Salvatore Mancuso Luca Cucullo |
| author_sort | Snehal Raut |
| collection | DOAJ |
| description | The brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain’s principal fuel source. Glucose transport across the blood–brain barrier (BBB) is primarily controlled via sodium-independent facilitated glucose transport, such as by glucose transporter 1 (GLUT1) and 3 (GLUT3). However, other glucose transporters, including GLUT4 and the sodium-dependent transporters SGLT1 and SGLT6, have been reported in vitro and in vivo. When the BBB endothelial layer is crossed, neurons and astrocytes can absorb the glucose using their GLUT1 and GLUT3 transporters. Glucose then enters the glycolytic pathway and is metabolized into adenosine triphosphate (ATP), which supplies the energy to support cellular functions. The transport and metabolism of glucose in the brain are impacted by several medical conditions, which can cause neurological and neuropsychiatric symptoms. Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, traumatic brain injury (TBI), schizophrenia, etc., are a few of the most prevalent disorders, characterized by a decline in brain metabolism or hypometabolism early in the course of the disease. Indeed, AD is considered a metabolic disorder related to decreased brain glucose metabolism, involving brain insulin resistance and age-dependent mitochondrial dysfunction. Although the conventional view is that reduced cerebral metabolism is an effect of neuronal loss and consequent brain atrophy, a growing body of evidence points to the opposite, where hypometabolism is prodromal or at least precedes the onset of brain atrophy and the manifestation of clinical symptoms. The underlying processes responsible for these glucose transport and metabolic abnormalities are complicated and remain poorly understood. This review article provides a comprehensive overview of the current understanding of hypometabolism in AD and potential therapeutic targets. |
| first_indexed | 2024-03-11T00:03:28Z |
| format | Article |
| id | doaj.art-8bf17d7f447446f5a3fb3414cfaab49e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:03:28Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8bf17d7f447446f5a3fb3414cfaab49e2023-11-19T00:36:09ZengMDPI AGCells2073-44092023-08-011216201910.3390/cells12162019Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An OverviewSnehal Raut0Aditya Bhalerao1Michael Powers2Minelly Gonzalez3Salvatore Mancuso4Luca Cucullo5Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USADepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USADepartment of Biological and Biomedical Sciences, Oakland University, Rochester, MI 48309, USADepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USADepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USADepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USAThe brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain’s principal fuel source. Glucose transport across the blood–brain barrier (BBB) is primarily controlled via sodium-independent facilitated glucose transport, such as by glucose transporter 1 (GLUT1) and 3 (GLUT3). However, other glucose transporters, including GLUT4 and the sodium-dependent transporters SGLT1 and SGLT6, have been reported in vitro and in vivo. When the BBB endothelial layer is crossed, neurons and astrocytes can absorb the glucose using their GLUT1 and GLUT3 transporters. Glucose then enters the glycolytic pathway and is metabolized into adenosine triphosphate (ATP), which supplies the energy to support cellular functions. The transport and metabolism of glucose in the brain are impacted by several medical conditions, which can cause neurological and neuropsychiatric symptoms. Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, traumatic brain injury (TBI), schizophrenia, etc., are a few of the most prevalent disorders, characterized by a decline in brain metabolism or hypometabolism early in the course of the disease. Indeed, AD is considered a metabolic disorder related to decreased brain glucose metabolism, involving brain insulin resistance and age-dependent mitochondrial dysfunction. Although the conventional view is that reduced cerebral metabolism is an effect of neuronal loss and consequent brain atrophy, a growing body of evidence points to the opposite, where hypometabolism is prodromal or at least precedes the onset of brain atrophy and the manifestation of clinical symptoms. The underlying processes responsible for these glucose transport and metabolic abnormalities are complicated and remain poorly understood. This review article provides a comprehensive overview of the current understanding of hypometabolism in AD and potential therapeutic targets.https://www.mdpi.com/2073-4409/12/16/2019glucose transporterblood–brain barrierAlzheimer’s diseaseglucose metabolismoxidative stressglucose uptake |
| spellingShingle | Snehal Raut Aditya Bhalerao Michael Powers Minelly Gonzalez Salvatore Mancuso Luca Cucullo Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview Cells glucose transporter blood–brain barrier Alzheimer’s disease glucose metabolism oxidative stress glucose uptake |
| title | Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview |
| title_full | Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview |
| title_fullStr | Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview |
| title_full_unstemmed | Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview |
| title_short | Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview |
| title_sort | hypometabolism alzheimer s disease and possible therapeutic targets an overview |
| topic | glucose transporter blood–brain barrier Alzheimer’s disease glucose metabolism oxidative stress glucose uptake |
| url | https://www.mdpi.com/2073-4409/12/16/2019 |
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